nivolumab/ipilimumab and chemotherapy combination in advanced nsclc patients with hiv, hbv, hcv and long covid syndrome

Conditions: NSCLC Stage IV; HIV; HBV; HCV; Long COVID

Summary: study type: phase 2 - interventional trial number of patients to be enrolled: 105 participating countries: italy study drugs: nivolumab and ipilimumab cohort a: hbv and hcv patients cohort b: hiv patients cohort c: long covid syndrome the stratification factors are hbv/hcv positive (cohort a), hiv positive (cohort b), patients with long covid syndrome (cohort c), histology (squamous vs non-squamous histology), and gender (male vs female).

participants (≥ 18 years) must have histologically confirmed metastatic or unresectable non-small cell lung cancer (both non-squamous and squamous), without sensitizing egfr, alk, ros1, braf and ntrk alterations, with chronic viral infections, such as hbv and hcv in cohort a and hiv in cohort b and with long covid syndrome in cohort c. the study is a multicenter, open-label trial designed according to bryant and day and including 1) a screening phase to establish study eligibility, 2) an open-label treatment phase, in which patients will receive nivolumab plus ipilimumab in combination with histology-based chemotherapy (2 induction cycles) to ascertain its safety, defined as incidence of grade 3 or 4 (g3/4) treatment-related adverse events (traes) and activity, 3) and a follow-up phase to monitor survival status and subsequent therapies. in detail, the study includes: 1. a screening phase to establish study eligibility (including, for example, the availability of tumour tissue for molecular analyses) and document baseline assessments. 2. an open-label treatment phase, in which patients will be treated with 2 cycles of chemotherapy and nivolumab plus ipilimumab until disease progression, unacceptable toxicity or for a maximum of 2 years. upon disease progression or completion of trial treatment, further therapy will be at the discretion of the treating physician. 3. a follow-up phase, to monitor safety, survival status and subsequent therapies.

Eligibility criteria:
inclusion criteria: * participants must have histologically confirmed diagnosis of metastatic or unresectable nsclc; * no sensitizing egfr, alk, ros1, braf and ntrk alterations; * eastern cooperative oncology group (ecog) score 0-1 (physically able to carry out light housework or office work through to being fully active as they were before cancer); * no prior systemic anticancer therapy; * tissue or programmed death-ligand 1 (pd-l1) results available; * hiv-1 or hiv-2 chronic infection, defined as i) a positive hiv 1-2 western blot or other fda/ce approved hiv confirmatory test (regardless the results of the hiv 1-2 screening test used \[2nd, 3rd, 4th generation tests, rapid tests or laboratory tests (i.e., elisa, eia, clia, etc.)\], ii) the referring physician's written record that hiv infection was documented, with supporting information on the participant's relevant medical history and/or current antiretroviral treatment for hiv infection; * only subjects with chronic or resolved hbv infections might be eligible. chronic hbv infections is defined as: the persistence of hbsag positivity for more than 6 months (regardless hbeag result, hbv-dna level and the presence of liver necroinflammation). resolved hbv infection is defined by: the absence of liver inflammation (clinically and laboratory), hbsag negativity and hbsab (anti-hbs antibodies) and hbcab (anti-hbc igg) positive result; * only subjects with resolved hcv infections might be eligible. subjects with a newly diagnosed chronic hcv infection (defined as: positive hcv antibodies + detectable hcv-rna) should be treated for hcv infection before enrollment. acute hcv infection \[defined as a positive hcv-rna and i) a negative serological hcv assay (hcv-ab) or ii) a positive serological hcv assay (hcv-ab) with a negative test 6 months earlier\] cannot be enrolled in the study. * patients with past hcv infection, with no evidence of chronic infection (i.e., anti-hcv antibody positivity, hcv-rna negativity) should be excluded; * patients with confirmed long covid syndrome or pasc defined, as suggest by world health organization (who), as "condition occurs in individuals with a history of probable or confirmed sars cov-2 infection, usually 3 months from the onset of covid-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis". this condition must be present at enrollment; * participants must have a nasopharyngeal swab positive for sars-cov2 within 12 months before enrolment; * participants must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatment; * participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography (ct) scan, magnetic resonance imaging (mri), or calipers by clinical exam; scans must have been performed within 4 weeks prior to registration. * women of childbearing potential (wocbp) must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours prior to the start of study drug; * ability to understand and to sign a written informed consent document. exclusion criteria: * eastern cooperative oncology group (ecog) score ≥2; * untreated symptomatic brain metastases or leptomeningeal metastases; * another active concomitant malignancy; * active, known or suspected, autoimmune disease; * active hbv or hcv infection, presence of any infectious disease requiring specific treatment. * active sars-cov2 infection.